Previous studies in several species have indicated that immune function declines with age and that thyroid hormone is required for maintenance of normal immune function. Other data suggest that tissue responsiveness to thyroid hormone decreases with age, raising the possibility that the age-related decline in immune function reflects, at least partly, a loss of response to thyroid hormone. We propose to explore the latter hypothesis, in the rat, first by examining the effect of age on the responsiveness of lymphoid tissue to triiodothyronine in vitro, using as response indices several metabolic functions that have been shown to be necessary for or related to the response to mitogenic agents and that we have shown to be stimulated by thyroid hormones in vitro. We also propose to examine, in animals of varying age, the response of these functions, as measured in vitro, to alterations of in vivo thyroid status. We propose, in addition, to examine once again whether the mitogenic response of lymphoid tissue does decrease with age, whether this is accompanied by an impaired metabolic response to mitogenesis, and whether these responses are altered by changes in in vivo thyroid states.